Nonspecific orbital inflammation (NSOI) is an inflammatory disease which causes pain, diplopia, and loss of vision. The pathogenesis of NSOI is largely unknown and virtually unstudied. Microarray analysis of gene expression has enjoyed marked success in providing novel insights into disease pathogenesis. In addition, microarray profiling has been used to identify distinct subsets of disease that in many instances are indistinguishable by histopathology. We propose to utilize microarray gene expression profiling from formalin- fixed, paraffin-embedded (FFPE) orbital biopsies to gain insight into the pathogenesis of NSOI. Gene expression patterns from orbital tissue of patients with NSOI will be compared with gene expression patterns from orbital biopsies from patients with thyroid orbitopathy, sarcoidosis, or Wegener's granulomatosis as well as patterns from normal orbital fat, normal lacrimal gland, or extraocular muscle. We hypothesize that patients with NSOI will have distinct patterns of gene expression that will provide insights into the pathogenesis of the disease. Furthermore, we hypothesize that NSOI is a heterogeneous collection of diseases and that this heterogeneity can be definitively demonstrated by gene expression profiling. Finally we hypothesize that gene expression profiling will help in prognostic and therapeutic decision making for patients with this highly morbid diagnosis. PUBLIC HEALTH RELEVANCE: Inflammation within the eye socket or orbit causes pain, double vision, and loss of vision. Several diseases including sarcoidosis, Wegener's granulomatous, Graves'disease (hyperthyroidism) and so called nonspecific orbital inflammatory disease can cause orbital inflammation. We have organized 14 centers from around the world to contribute previously biopsied tissue to analyze tissue patterns of gene expression from patients with orbital inflammation in order to clarify the cause, predict prognosis, and ultimately improve the therapy.